Bile acid-independent protection against Clostridioides difficile infection.

Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the pro...

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Autores principales:	Andrea Martinez Aguirre, Nazli Yalcinkaya, Qinglong Wu, Alton Swennes, Mary Elizabeth Tessier, Paul Roberts, Fabio Miyajima, Tor Savidge, Joseph A Sorg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a68d3cc2a7c4485c800df500d3fb295e
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spelling	oai:doaj.org-article:a68d3cc2a7c4485c800df500d3fb295e2021-12-02T20:00:00ZBile acid-independent protection against Clostridioides difficile infection.1553-73661553-737410.1371/journal.ppat.1010015https://doaj.org/article/a68d3cc2a7c4485c800df500d3fb295e2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1010015https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.Andrea Martinez AguirreNazli YalcinkayaQinglong WuAlton SwennesMary Elizabeth TessierPaul RobertsFabio MiyajimaTor SavidgeJoseph A SorgPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1010015 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Andrea Martinez Aguirre Nazli Yalcinkaya Qinglong Wu Alton Swennes Mary Elizabeth Tessier Paul Roberts Fabio Miyajima Tor Savidge Joseph A Sorg Bile acid-independent protection against Clostridioides difficile infection.
description	Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.
format	article
author	Andrea Martinez Aguirre Nazli Yalcinkaya Qinglong Wu Alton Swennes Mary Elizabeth Tessier Paul Roberts Fabio Miyajima Tor Savidge Joseph A Sorg
author_facet	Andrea Martinez Aguirre Nazli Yalcinkaya Qinglong Wu Alton Swennes Mary Elizabeth Tessier Paul Roberts Fabio Miyajima Tor Savidge Joseph A Sorg
author_sort	Andrea Martinez Aguirre
title	Bile acid-independent protection against Clostridioides difficile infection.
title_short	Bile acid-independent protection against Clostridioides difficile infection.
title_full	Bile acid-independent protection against Clostridioides difficile infection.
title_fullStr	Bile acid-independent protection against Clostridioides difficile infection.
title_full_unstemmed	Bile acid-independent protection against Clostridioides difficile infection.
title_sort	bile acid-independent protection against clostridioides difficile infection.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a68d3cc2a7c4485c800df500d3fb295e
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Bile acid-independent protection against Clostridioides difficile infection.

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